1. Technical Field
The present disclosure relates to vectors comprising Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 gene and non-human animals in which the expression of hnRNP A1 gene has been disrupted.
2. Description of Related Art
Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is a protein that has been reported to play a significant part in regulating the process of gene splicing (Del Gatto-Konczak et al., 1999 MOI Cell Biol 19, 251-260), telomere extension (LaBranche et al., 1998 Nat Genet 19, 199-202), and viral replication (Lin et al., 2009 J Virol 83, 6106-6114; Monette et al., 2009, J Biol Chem 284, 31350-31362), and any of the identified cellular events has been implicated with diseases including cancerous progression carcinogenesis, and neurodegenerative disease.
Recently, hnRNP A1 is identified to be involved in alternative splicing of many disease-related proteins, such as GTPase Rac1 and carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1). Rac1b, an alternatively spliced isoform of Rac1, was originally identified as an over-expressed protein in breast and colorectal cancer cells, and has subsequently been suggested an important role in many oncogenic signaling pathways. CEACAM1 is expressed in a variety of cell types, including breast cancer cells, and is also implicated in carcinogenesis. Alternative splicing of Exon 11 of the insulin receptor gene (INSR), which is developmental stage-dependent and tissue-specific, is also regulated by hnRNP A1. hnRNP A1 inhibites exon 11 inclusion and results in insulin receptor-B (IR-B) expression, which predominantly express in insulin-sensitive tissue, suggesting a metabolic role (Talukdar et al., PLoS One (2011), 6: e27869). It is demonstrated that hnRNP A1 is a negative factor to splicing selection of Ataxia Teleangectasia Mutated gene (ATM), the gene mutated in an autosomal recessive disorder characterized by cerebellar ataxia and oculocutaneous telangiectasias (Pastor et al., PLoS One (2011), 6: e23349).
In view of the role of hnRNP A1 associated with various diseases, it is useful to provide an animal model, particularly, a hnRNP A1 knockout model, in which the expression level of hnRNP A1 protein is not expressed in null mice and the expression level of hnRNP A1 in the heterozygous in the knockout model is relatively low, as compared to a normal animal, for further studies on the function of hnRNP A1 gene in any of the identified diseases and its use in developing therapies to treat any of these diseases.